This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Proper copper homeostasis is essential for life, and all cells respond to toxic copper excess or copper starvation by inducing transcriptional programs that will result in sequestration of excess copper or uptake of extracellular copper, as needed. Excess free copper ions result in generation of reactive oxygen species (ROS). ROS are a major source of damage to cellular macromolecules, including DNA. The yeast CUP1 gene encodes a copper-binding metallothionein that is required for survival in the presence of toxic copper levels. CUP1 induction requires the copper-sensing activator Ace1 and the chromatin remodeler SWI/SNF, and the CUP1 promoter is subject to dynamic histone acetylation. CUP1 transcription is also rapidly shut down after the initial copper response. This autoregulation is an active process, which involves not only release of Ace1 but also the continued presence of SWI/SNF. We have also identified a CUP1 antisense transcript, RUF5, which is transcribed during CUP1 shutdown. The goal of this study is to understand how chromatin structure and modification regulate the CUP1 transcription cycle, and to explore the role of the RUF5 transcript in CUP1 expression.